Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma.

BACKGROUND: Circulating tumor cell (CTC) count and neutrophil-to-lymphocyte ratio (NLR) are both closely associated with the prognosis of hepatocellular carcinoma (HCC). AIM: To investigate the prognostic value of combining these two indicators in HCC. METHODS: Clinical data were collected from patients with advanced HCC who received immune therapy combined with targeted therapy at the Department of Oncology, the Affiliated Hospital of Southwest Medical University, Sichuan, China, from 2021 to 2023. The optimal cutoff values for CTC programmed death-ligand 1 (PD-L1) (+) > 1 or CTC PD-L1 (+) ≤ 1 and NLR > 3.89 or NLR ≤ 3.89 were evaluated using X-Tile software. Patients were categorized into three groups based on CTC PD-L1 (+) counts and NLR: CTC-NLR (0), CTC-NLR (1), and CTC-NLR (2). The relationship between CTC-NLR and clinical variables as well as survival rates was assessed. RESULTS: Patients with high CTC PD-L1 (+) expression or NLR at baseline had shorter median progression-free survival (mPFS) and median overall survival (mOS) than those with low levels of CTC PD-L1 (+) or NLR (P < 0.001). Meanwhile, patients in the CTC-NLR (2) group showed a significant decrease in mPFS and mOS. Cox regression analysis revealed that alpha-fetoprotein (AFP), CTC PD-L1 (+), and CTC-NLR were independent predictors of OS. The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months (0.821) and 18 months (0.821) was superior to that of AFP and CTC PD-L1 (+). CONCLUSION: HCC patients with high CTC PD-L1 (+) or NLR expression tend to exhibit poor prognosis, and a high baseline CTC-NLR score may indicate low survival. CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

An ethanolic extract of Arctium lappa L. leaves ameliorates experimental atherosclerosis by modulating lipid metabolism and inflammatory responses through PI3K/Akt and NF-κB singnaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS), a lipid-induced inflammatory condition of the arteries, is a primary contributor to atherosclerotic cardiovascular diseases including stroke. Arctium lappa L. leaf (ALL), an edible and medicinal herb in China, has been documented and commonly used for treating stroke since the ancient times. However, the elucidations on its anti-AS effects and molecular mechanism remain insufficient. AIM OF THE STUDY: To investigate the AS-ameliorating effects and the underlying mechanism of action of an ethanolic extract of leaves of Arctium lappa L. (ALLE). MATERIALS AND METHODS: ALLE was reflux extracted using with 70% ethanol. An HPLC method was established to monitor the quality of ALLE. High fat diet (HFD) and vitamin D3-induced experimental AS in rats were used to determine the in vivo effects; and oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro assays. Simvatatin was used as positive control. Biochemical assays were implemented to ascertain the secretions of lipids and pro-inflammatory mediators. Haematoxylin-eosin (H&E) and Oil red O stains were employed to assess histopathological alterations and lipid accumulation conditions, respectively. CCK-8 assays were used to measure cytotoxicity. Immunoblotting assay was conducted to measure protein levels. RESULTS: ALLE treatment significantly ameliorated lipid deposition and histological abnormalities of aortas and livers in AS rats; improved the imbalances of serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); notably attenuated serum concentrations of inflammation-associated cytokines/molecules including TNF-α, IL-6, IL-1ß, VCAM-1, ICAM-1and MMP-9. Mechanistic studies demonstrated that ALLE suppressed the phosphorylation/activation of PI3K, Akt and NF-κB in AS rat aortas and in cultured foam cells. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of ALLE on lipid deposition, productions of TC, TNF-α and IL-6, and protein levels of molecules of PI3K/Akt and NF-κB singnaling pathways. CONCLUSIONS: ALLE ameliorates HFD- and vitamin D3-induced experimental AS by modulating lipid metabolism and inflammatory responses, and underlying mechanisms involves inhibition of the PI3K/Akt and NF-κB singnaling pathways. The findings of this study provide scientific justifications for the traditional application of ALL in managing atherosclerotic diseases.

Magnetic resonance imaging radiomics-based prediction of clinically significant prostate cancer in equivocal PI-RADS 3 lesions in the transitional zone.

Purpose: This bi-institutional study aimed to establish a robust model for predicting clinically significant prostate cancer (csPCa) (pathological grade group ≥ 2) in PI-RADS 3 lesions in the transition zone by comparing the performance of combination models. Materials and methods: This study included 243 consecutive men who underwent 3-Tesla magnetic resonance imaging (MRI) and ultrasound-guided transrectal biopsy from January 2020 and April 2022 which is divided into a training cohort of 170 patients and a separate testing cohort of 73 patients. T2WI and DWI images were manually segmented for PI-RADS 3 lesions for the mean ADC and radiomic analysis. Predictive clinical factors were identified using both univariate and multivariate logistic models. The least absolute shrinkage and selection operator (LASSO) regression models were deployed for feature selection and for constructing radiomic signatures. We developed nine models utilizing clinical factors, radiological features, and radiomics, leveraging logistic and XGboost methods. The performances of these models was subsequently compared using Receiver Operating Characteristic (ROC) analysis and the Delong test. Results: Out of the 243 participants with a median age of 70 years, 30 were diagnosed with csPCa, leaving 213 without a csPCa diagnosis. Prostate-specific antigen density (PSAD) stood out as the only significant clinical factor (odds ratio [OR], 1.068; 95% confidence interval [CI], 1.029-1.115), discovered through the univariate and multivariate logistic models. Seven radiomic features correlated with csPCa prediction. Notably, the XGboost model outperformed eight other models (AUC of the training cohort: 0.949, and validation cohort: 0.913). However, it did not surpass the PSAD+MADC model (P > 0.05) in the training and testing cohorts (AUC, 0.949 vs. 0.888 and 0.913 vs. 0.854, respectively). Conclusion: The machine learning XGboost model presented the best performance in predicting csPCa in PI-RADS 3 lesions within the transitional zone. However, the addition of radiomic classifiers did not display any significant enhancement over the compound model of clinical and radiological findings. The most exemplary and generalized option for quantitative prostate evaluation was Mean ADC+PSAD.

Exploring the adaptive leisure activities of classified nursing model in elderly colon cancer patients: a perspective on interactive care.

OBJECTIVE: The aims of the study were first to explore the adaptive leisure activities of classified nursing model from the perspective of nurse-patient interactive care, and to explore its impact on the physical and mental health of patients with colon cancer. METHODS: From September 2017 to March 2022 as the observation time node, 82 patients with colon cancer who met the established inclusion and exclusion criteria were regarded as the research objects through the random number table as the grouping tool. The two groups of patients were named as the research group and the control group, with 41 patients in each group. The control group implemented routine nursing measures, and the research group implemented classified nursing mode and adaptive leisure activity mode. The two groups of patients received 4 weeks of nursing intervention. With the help of self-rating anxiety scale, self-rating depression scale, self-care ability evaluation scale and health status survey brief form, the two groups of patients were compared before intervention and at the end of the 4th week after intervention. RESULTS: After the intervention, the anxiety score (t = 6.656, p < 0.001) and depression score (t = 4.851, p < 0.001) of the research group were lower than those of the control group, and the difference was statistically significant. After the intervention, the self-concept (t = 4.845, p < 0.001), self-responsibility (t = 6.071, p < 0.001), self-care skills (t = 3.341, p < 0.001), health knowledge (t = 3.698, p < 0.001) and total score (t = 9.246, p < 0.001) of the research group were higher than those of the control group, and the difference was statistically significant. After the intervention, physical functioning (t = 8.141, p < 0.001), bodily pain (t = 6.083, p < 0.001), general health (t = 9.424, p < 0.001), role-physical (t = 8.057, p < 0.001), role-emotional (t = 13.252, p < 0.001), mental health (t = 12.565, p < 0.001), social functioning (t = 10.813, p < 0.001) and vitality score (t = 12.890, p < 0.001) of the research group were higher than those of the control group, with significant differences. CONCLUSION: Interactive care through adaptive leisure nursing improves mental well-being, self-management, and psychosocial functioning in elderly colon cancer patients, promoting overall health.

DFT + U Simulation of the X-ray Absorption Near-Edge Structure of Bulk UO2 and PuO2.

Hubbard U-corrected density functional theory within the periodic boundary condition model in the WIEN2k code is used to simulate the actinide LIII and O K edge X-ray absorption near-edge structure (XANES) for UO2 and PuO2. Spin-orbit coupling effects are included, as are possible excitonic effects using supercells with a core hole on one of the atoms. Our calculations yield spectra in excellent agreement with previous experiments and superior to previous simulations. Density of states analysis reveals the mechanism behind the XANES peaks: the main contribution to the U/Pu LIII edges comes from the U/Pu d states hybridized with O p states, while as expected, the O p states primarily determine the O K edges of both UO2 and PuO2. The O K edges also feature O p hybridizing with U/Pu d and f states in the low-energy region and with U/Pu s and p states for the higher-energy peaks.

Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia.

OBJECTIVE: To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI). METHODS: First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro. RESULTS: MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model. CONCLUSIONS: THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones.

[Nomographic Model for Predicting Severe Foot Pain in Nurses from Tertiary Hospitals in China].

Objective: To investigate the prevalence and common sites of severe foot pain among nurses, to define the risk factors of severe foot pain in nurses in tertiary hospital in China, and to construct a nomograph model for predicting individuals' risks for severe foot pain. Methods: Between August 2019 and December 2019, a stratified global sampling method was used to select 10691 nurses from 351 tertiary hospitals in China to investigate the incidence of severe foot pain among them. The variables that may affect the occurrence of severe foot pain were analyzed by single factor analysis to identify the influencing factors of severe foot pain in nurses. Furthermore, the independent risk factors of severe foot pain were analyzed by stepwise logistic regression analysis. The statistically significant factors identified in the multivariate regression analysis were incorporated into the nomograph prediction model. The predictive performance of the nomograph was measured by the consistency index (C-index) and calibrated with 1000 Bootstrap samples. Results: A total of 3419 nurses out of the 10691 had foot pain, resulting in an incidence of 31.98%. The incidence of severe pain (VAS score 7-10) was 2.27% (243 of 10691). The locations of severe pain were more commonly found in the soles and heels of both feet. Six factors, including age, education, the material of the work shoes, comfortableness of the work shoes, number of complications, and foot injure history, were incorporated in the nomograph predicting model. The C-index value was 0.706 and the standard curve fitted well with the calibrated prediction curve. Conclusion: The risk prediction model constructed in this study showed sound performance in predicting the risk of severe foot pain in nurses, and all the indicators involved are simple and the relevant data are easily obtained. The model can provide reference for preventing severe foot pain in nurses.

Different types of fruit intake and colorectal cancer risk: A meta-analysis of observational studies.

BACKGROUND: Multiple studies investigating the relationship between intake of different types of fruit and colorectal cancer (CRC) risk have yielded inconsistent results. AIM: To perform a meta-analysis of existing studies to assess the association between the intake of different kinds of fruit and the incidence of CRC. METHODS: We searched online literature databases including PubMed, Embase, WOS, and Cochrane Library for relevant articles available up to August 2022. With data extracted from observational studies, odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using random-effects models. A funnel plot and Egger's test were used to determine publication bias. Furthermore, subgroup analysis and dose-response analysis were performed. All analyses were conducted using R (version 4.1.3). RESULTS: Twenty-four eligible studies involving 1068158 participants were included in this review. The meta-analysis showed that compared to a low intake, a higher intake of citrus, apples, watermelon, and kiwi reduced the risk of CRC by 9% [OR (95%CI) = 0.91 (0.85-0.97)], 25% [OR (95%CI) = 0.75 (0.66-0.85)], 26% [OR (95%CI) = 0.74 (0.58-0.94)], 13% [OR (95%CI) = 0.87 (0.78-0.96)], respectively. No significant association was observed between the intake of other types of fruit and the risk of CRC. In the dose-response analysis, a nonlinear association was found [R (95%CI) = -0.0031 (-0.0047 to -0.0014)] between citrus intake and CRC risk (P < 0.001), with the risk minimized around 120 g/d (OR = 0.85), while no significant dose-response correlation was observed after continued increase in intake. CONCLUSION: We found that a higher intake of citrus, apples, watermelon, and kiwi was negatively associated with the risk of CRC, while the intake of other types of fruits were not significantly associated with CRC. Citrus intake showed a non-linear dose-response relationship with the risk of CRC. This meta-analysis provides further evidence that a higher intake of specific types of fruit is effective in preventing the occurrence of CRC.

[Echinacoside hampers malignant progression of breast cancer MCF-7 cells by modulating AKR1B10/ERK signal transduction].

This study analyzes the impact of echinacoside(ECH) in the proliferation, metastasis and adriamycin(ADR) resistance of breast cancer(BC) MCF-7 cells via the modulation of aldo-keto reductase family 1 member 10(AKR1B10)/extracellular signal-regulated kinase(ERK) pathway. The chemical structure of ECH was firstly confirmed. MCF-7 cells were treated with different concentration(0, 10, 20, 40 µg·mL~(-1)) of ECH for 48 h. Western blot was used to analyze expression of AKR1B10/ERK pathway-associated proteins and cell counting kit-8(CCK-8) assay to determine cell viability. MCF-7 cells were collected and classified into control group, ECH group, ECH + Ov-NC group, and ECH + Ov-AKR1B10 group. Then Western blot was employed to analyze the expression of AKR1B10/ERK pathway-associated proteins. CCK-8 and 5-ethynyl-2'-deoxyuridine(EdU) assay were used to examine cell proliferation. Cell migration was appraised with scratch assay, Transwell assay, and Western blot. Eventually, MCF-7 cells were treated with ADR for 48 h to induce ADR resistance. Cell viability was tested by CCK-8 assay and cell apoptosis was estimated based on terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay and Western blot. Based on Protein Data Bank(PDB) and molecular docking, the binding affinity of ECH to AKR1B10 was assessed. Various doses of ECH decreased the expression of AKR1B10/ERK pathway-associated proteins in a dose-dependent manner and declined cell viability compared with the control group. Compared with the control group, 40 µg·mL~(-1) ECH blocked the AKR1B10/ERK pathway in MCF-7 cells and inhibited the proliferation, metastasis and ADR resistance of the cells. Compared with the ECH + Ov-NC group, ECH + Ov-AKR1B10 group showed the recovery of some biological behaviors of MCF-7 cells. ECH also targeted AKR1B10. ECH can inhibit the proliferation, metastasis, and ADR resistance of BC cells by blocking AKR1B10/ERK pathway.

Anti-carbonic anhydrase II antibody reflects urinary acidification defect especially in proximal renal tubules in patients with primary Sjögren syndrome.

Primary Sjögren syndrome (pSS) is a systemic autoimmue disease featured by excessive autoantibody production. It has been demonstrated that anti-carbonic anhydrase II (anti-CA II) antibody is correlated with renal tubular acidosis in pSS; however, no further details about urinary acidification defect have been reported, and the antibody's relationship with other organ impairments remains unknown. This case-control study aimed to examine anti-CA II antibody levels in relation to various systemic complications in pSS, and evaluate its potential role as a organ-specific biomarker in a Chinese cohort. Serum anti-CA II antibody levels were determined using ELISA in 123 patients with pSS and 72 healthy controls. The medical records of the patients were collected, and the correlation between serum anti-CA II antibody and clinical/immunological parameters was investigated. Serum anti-CA II antibody level and its positive rate were significantly increased in pSS patients compared with controls, and ANA-positive patients presented even higher titers of the antibody. In anti-CA II positive group, remarkably higher urine pH and bicarbonate, as well as lower urine titratable acid and serum potassium were observed, which indicated renal tubular acidification dysfunction both involving bicarbonate reabsorption and acid secretion. In addition, platelet count and complement 3, complement 4 levels decreased, whereas serum IgG, IgA and γ-globulin levels increased notably in accord with a higher EULAR SS disease activity index score in these patients. Further analysis showed that anti-CA II antibody was most elevated in patients with defect in bicarbonate reabsorption, reflecting proximal renal tubular injury, rather than in patients with distal renal tubular acidosis as previously reported. In conclusion, anti-CA II antibody reflects renal (especially proximal renal tubular) and hematologic impairment as well as increased disease activity in pSS. It may act as a serum biomarker of systemic damage of pSS.

14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-κB/Sirtuin 2-NLRP3-mediated adipose tissue remodeling.

Interleukin (IL)-1ß is a culprit of adipose tissue inflammation, which in turn causes systematic inflammation and insulin resistance in obese individuals. IL-1ß is mainly produced in monocytes and macrophages and marginally in adipocytes, through cleavage of the inactive pro-IL-1ß precursor by caspase-1, which is activated via the NLRP3 inflammasome complex. The nuclear factor-κB (NF-κB) transcription factor is the master regulator of inflammatory responses. Brindle berry (Garcinia cambogia) has been widely used as health products for treating obesity and related metabolic disorders, but its active principles remain unclear. We previously found a series of polyisoprenylated benzophenones from brindle berry with anti-inflammatory activities. In this study we investigated whether 14-deoxygarcinol (DOG), a major polyisoprenylated benzophenone from brindle berry, alleviated adipose tissue inflammation and insulin sensitivity in high-fat diet fed mice. The mice were administered DOG (2.5, 5 mg · kg-1 · d-1, i.p.) for 4 weeks. We showed that DOG injection dose-dependently improved insulin resistance and hyperlipidemia, but not adiposity in high-fat diet-fed mice. We found that DOG injection significantly alleviated adipose tissue inflammation via preventing macrophage infiltration and pro-inflammatory polarization of macrophages, and adipose tissue fibrosis via reducing the abnormal deposition of extracellular matrix. In LPS plus nigericin-stimulated THP-1 macrophages, DOG (1.25, 2.5, 5 µM) dose-dependently suppressed the activation of NLRP3 inflammasome and NF-κB signaling pathway. We demonstrated that DOG bound to and activated the deacetylase Sirtuin 2, which in turn deacetylated and inactivated NLRP3 inflammasome to reduce IL-1ß secretion. Moreover, DOG (1.25, 2.5, 5 µM) dose-dependently mitigated inflammatory responses in macrophage conditioned media-treated adipocytes and suppressed macrophage migration toward adipocytes. Taken together, DOG might be a drug candidate to treat metabolic disorders through modulation of adipose tissue remodeling.

Mid-term outcomes of microfragmented adipose tissue plus arthroscopic surgery for knee osteoarthritis: A randomized, active-control, multicenter clinical trial.

BACKGROUND: Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases. AIM: To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA). METHODS: A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group (n = 151, were administered MFAT following arthroscopic surgery), or the control group (n = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline. RESULTS: The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline (P < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group (P < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo (P < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo (P = 0.367). No serious adverse events occurred in both groups. CONCLUSION: The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA.

Unexpected assembly machinery for 4(3H)-quinazolinone scaffold synthesis.

4(3H)-quinazolinone is the core scaffold in more than 200 natural alkaloids and numerous drugs. Many chemosynthetic methodologies have been developed to generate it; however, investigation of its native enzymatic formation mechanism in fungi has been largely limited to fumiquinazolines, where the two nitrogen atoms come from anthranilate (N-1) and the α-NH2 of amino acids (N-3). Here, via biochemical investigation of the chrysogine pathway, unexpected assembly machinery for 4(3H)-quinazolinone is unveiled, which involves a fungal two-module nonribosomal peptide synthase ftChyA with an unusual terminal condensation domain catalysing tripeptide formation; reveals that N-3 originates from the inorganic ammonium ions or the amide of L-Gln; demonstrates an unusual α-ketoglutarate-dependent dioxygenase ftChyM catalysis of the C-N bond oxidative cleavage of a tripeptide to form a dipeptide. Our study uncovers a unique release and tailoring mechanism for nonribosomal peptides and an alternative route for the synthesis of 4(3H)-quinazolinone scaffolds.

SLC25A25-AS1 over-expression could be predicted the dismal prognosis and was related to the immune microenvironment in prostate cancer.

It has been established that long-chain coding RNA (lncRNA) SLC25A25-AS1 is associated with cancer progression. However, the roles and mechanisms of SLC25A25-AS1 in prostate cancer (PC) have not been reported in the literature. The present study explored the relationship between SLC25A25-AS1 expression and PC progression via comprehensive analysis. The pan-cancer expression of SLC25A25-AS1 was identified using data from The Cancer Genome Atlas (TCGA) database and tissue specimens from our hospital. The expression levels of SLC25A25-AS1 in various subgroups based on the clinical features were identified. The prognostic value of SLC25A25-AS1 and SLC25A25-AS1 co-expressed lncRNAs in PC patients was assessed by survival analysis and ROC analysis, and prognosis-related risk models of SLC25A25-AS1 were constructed. The relationship between SLC25A25-AS1 and the PC immune microenvironment was investigated using correlation analysis. SLC25A25-AS1 expression in PC was significantly increased and correlated with the T stage, clinical stage, Gleason score (GS), and dismal prognosis. SLC25A25-AS1 overexpression exhibited good performance in evaluating the prognosis of PC patients. The area under the curves (AUCs) of the 1-, 3-, and 5-year overall survival (OS) for SLC25A25-AS1 was 1, 0.876, and 0.749. Moreover, the AUCs for the 1-, 3-, and 5-year progress free interval (PFI) for SLC25A25-AS1 were 0.731, 0.701, and 0.718. SLC25A25-AS1 overexpression correlated with the infiltration of CD8 T cells, interstitial dendritic cells (IDC), macrophages and other cells. AC020558.2, ZNF32-AS2, AP4B1-AS1, AL355488.1, AC109460.3, SNHG1, C3orf35, LMNTD2-AS1, and AL365330.1 were significantly associated with SLC25A25-AS1 expression, and short OS and PFI in PC patients. The risk models of the SLC25A25-AS1-related lncRNAs were associated with a dismal prognosis in PC. Overall, SLC25A25-AS1 expression was increased in PC and related to the prognosis and PC immune microenvironment. The risk model of SLC25A25-AS1 have huge prospect for application as prognostic tools in PC.

DFT + U Study of Uranium Dioxide and Plutonium Dioxide with Occupation Matrix Control.

DFT + U with occupation matrix control (OMC) is applied to study computationally bulk UO2 and PuO2, the latter for the first time. Using the PBESol functional in conjunction with OMC locates AFM and NM ground states for UO2 and PuO2, respectively, in agreement with experimental findings. By simulating the lattice parameter, magnetic moment, band gap, and densities of states, U = 4.0 eV is recommended for AFM UO2, yielding data close to experiments for all considered properties. U = 4.5 and 4.0 eV are recommended for NM and AFM PuO2, respectively, though much larger U values (c. 10 eV) are required to yield the most recently reported PuO2 band gap. For both oxides, several excited states have similar properties to the ground state, reinforcing the need to employ OMC wherever possible.

Pediatric asthma control during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: With the onset of the coronavirus disease 2019 (COVID-19) pandemic, many experts expected that asthma-associated morbidity because of severe acute respiratory syndrome coronavirus 2 infection would dramatically increase. However, some studies suggested that there was no apparent increasing in asthma-related morbidity in children with asthma, it is even possible children may have improved outcomes. To understand the relationship between the COVID-19 pandemic and asthma outcomes, we performed this article. METHODS: We searched PubMed, Embase, and Cochrane Library to find literature from December 2019 to June 2021 related to COVID-19 and children's asthma control, among which results such as abstracts, comments, letters, reviews, and case reports were excluded. The level of asthma control during the COVID-19 pandemic was synthesized and discussed by outcomes of asthma exacerbation, emergency room visit, asthma admission, and childhood asthma control test (c-ACT). RESULTS: A total of 22,159 subjects were included in 10 studies. Random effect model was used to account for the data. Compared with the same period before the COVID-19 pandemic, asthma exacerbation reduced (odds ratio [OR] = 0.26, 95% confidence interval [CI] = [0.14-0.48], Z = 4.32, p < 0.0001), the odds of emergency room visit decreased as well (OR = 0.11, 95% CI = [0.04-0.26], Z = 4.98, p < 0.00001). The outcome of asthma admission showed no significant difference (OR = 0.84, 95% CI = [0.32-2.20], Z = 0.36, p = 0.72). The outcome of c-ACT scores were not analyzed because of the different manifestations used. Overall, c-ACT scores reduced during the pandemic. CONCLUSION: Compared to the same period before the COVID-19 pandemic, the level of asthma control has been significantly improved. We need to understand the exact factors leading to these improvements and find methods to sustain it.

Ainsliadimer C, a disesquiterpenoid isolated from Ainsliaea macrocephala, ameliorates inflammatory responses in adipose tissue via Sirtuin 1-NLRP3 inflammasome axis.

Interleukin-1ß (IL-1ß), a key pro-inflammatory cytokine, is majorly produced by macrophages through NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, which has been identified as the culprit to deteriorate the inflammatory crosstalk between macrophages and adipocytes. Ainsliadimer C (AC) is a disesquiterpenoid isolated from Ainsliaea macrocephala. In the current study, we investigated the effects of AC on adipose tissue inflammation in co-culture of macrophages and adipocytes in vitro as well as in LPS-treated mice in vivo. We showed that AC (20-80 µM) dose-dependently inhibited the secretion of IL-1ß from LPS plus ATP-stimulated THP-1 macrophages by inhibiting the activation of NLRP3 inflammasome. Furthermore, we found that AC treatment activated NAD+-dependent deacetylase Sirtuin 1 (SIRT1), resulting in reduced acetylation level of NLRP3. Molecular modeling analysis revealed that binding of AC to sirtuin-activating compound-binding domain increased the affinity of the substrate to the catalytic domain of SIRT1. Moreover, AC (80 µM) significantly attenuated macrophage-conditioned medium-induced inflammatory responses in 3T3-L1 adipocytes. In LPS-induced acute inflammatory mice, administration of AC (20, 60 mg·kg-1·d-1, ip) for 5 days significantly suppressed the pro-inflammatory cytokine levels in serum and epididymal white adipose tissue (eWAT), attenuated macrophage infiltration into eWAT, and mitigated adipose tissue inflammation. The beneficial effects of AC were blocked by co-administration of a selective SIRT1 inhibitor EX-527 (10 mg·kg-1·d-1). Taken together, AC suppresses NLRP3-mediated IL-1ß secretion through activating SIRT1, leading to attenuated inflammation in macrophages and adipose tissue, which might be a candidate to treat obesity-associated metabolic diseases.

Femoral and tibial cementless fixation neither increases blood loss nor impedes early functional recovery: A randomized controlled trial.

Background: Whether cementless fixation on femoral and tibial components increases blood loss during total knee arthroplasty (TKA) is unclear. The purpose of this randomized controlled trial was to compare blood loss and early functional recovery between patients who underwent cementless or cemented TKA. Methods: Between November 2021 and April 2022, sixty-one eligible patients at our medical center were randomized to cementless and cemented group. The primary outcome was total blood loss (TBL). Secondary outcomes were drainage, knee swelling, anemia, transfusion, hematological indicators, early functional recovery, and postoperative complications. The early functional recovery included range of motion (ROM), Hospital for Special Surgery (HSS) score, walking distance. Results: A total of 61 patients were analyzed, of whom 30 underwent cementless fixation. On postoperative day 1, the mean TBL was 394.39 ml (SD 182.97 ml) in the cementless group and 382.41 ml (SD 208.67 ml) in the cemented group (P = 0.863). By postoperative day 3, the corresponding mean TBL was higher at 593.48 ml (SD 230.04 ml) and 603.80 ml (SD 213.16 ml) (P = 0.751). The two groups did not differ significantly in drainage, knee swelling, anemia, levels of hemoglobin or hematocrit or platelets, ROM, HSS score, walking distance, or rates of transfusion or postoperative complications. Conclusions: Cementless fixation on femoral and tibial components during TKA does not increase blood loss or impede early functional recovery, which suggests that clinicians need not worry about blood loss and early functional recovery when deciding what type of fixation to perform during TKA. Trial registration: Number: ChiCTR2100052857; Date: November 6, 2021.

[Molecular mechanism of luteolin regulating lipoxygenase pathway against oxygen-glucose deprivation/reperfusion injury in H9c2 cardiomyocytes based on molecular docking].

The aim of this study was to investigate the mechanism of luteolin regulating lipoxygenase pathway against oxygen-glucose deprivation/reperfusion(OGD/R) injury in H9 c2 cardiomyocytes. First, Discovery Studio 2019 was used for the molecular docking of luteolin with three key enzymes including lipoxygenase 5(ALOX5), lipoxygenase 12(ALOX12), and lipoxygenase 15(ALOX15) in lipoxygenase pathway. The docking results showed that luteolin had high docking score and similar functional groups with the original ligand. From this, H9 c2 cardiomyocytes were cultured in vitro, and then the injury model of H9 c2 cardiomyocytes was induced by deprivation of oxygen-glucose for 8 h, and rehabilitation of oxygen-glucose for 12 h. Cell viability was detected by tetrazolium(MTT) colorimetry. H9 c2 cardiomyocytes were observed with a fluorescence inverted microscope, and colorimetry was used to detect the level of lactate dehydrogenase(LDH) in cell supernatant. The results showed that luteolin could significantly protect the morphology of H9 c2 cells, significantly improve the survival rate of H9 c2 cardiomyocytes in OGD/R injury model, reduce the level of LDH in cell supernatant, inhibit cytotoxicity, and maintain the integrity of cell membrane. The inflammatory cytokines interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay. Compared with the model group, luteolin can significantly reduce the release of IL-6 and TNF-α. Western blot was employed to detect the protein levels of ALOX5, ALOX12, and ALOX15 in lipoxygenase pathway. After luteolin intervention, the protein levels of ALOX5, ALOX12, and ALOX15 were significantly down-regulated compared with those in model group. These results indicate that luteolin can inhibit the release of IL-6 and TNF-α by restraining the activation of lipoxygenase pathway, thereby playing a protective role in the cardiomyocyte injury model induced by OGD/R.